We present models for the interstellar medium in disk galaxies. In particular, we investigate whether the ISM in low surface brightness galaxies can support a significant fraction of molecular gas given their low metallicity and surface density. It is found that the abundance and line brightness of CO in LSB galaxies is small and typically below current observational limits. Still, depending on physical details of the ISM, the fraction of gas in the form of molecular hydrogen can be significant in the inner few kpc of a low surface brightness galaxy. This molecular gas would be at temperatures of ~ 30 - 50 K, rather higher than in high surface brightness galaxies. These results may help explain the star forming properties and inferred evolutionary history of LSB galaxies.